Original Article
Correlation of CD4+ T cell Count with Total Lymphocyte Count, Haemoglobin and Erythrocyte Sedimentation Rate Levels in Human Immunodeficiency Virus Type-1 Disease

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Abstract

Background

Studies in human immunodeficiency virus (HIV) infected adults have demonstrated association of total lymphocyte count (TLC) <1200/mm3 and subsequent disease progression or mortality. The association of other surrogate makers such as haemoglobin (Hb), and erythrocyte sedimentation rate (ESR) with CD4 count and disease progression has also been suggested. This study was carried out to determine the relationship of CD4-positive T lymphocyte counts with TLC, Hb and ESR in HIV-infected individuals.

Methods

The study population comprised of 215 antiretroviral treatment naïve HIV-1 infected adults. The CD4 positive T cell counts, TLC, Hb and ESR of study participants were measured. Spearman's rank order correlation and Receiver Operating Characteristic were used for statistical analyses.

Result

The sensitivity, specificity, positive and negative likelihood ratios for cut-off value of TLC <1200/mm3 for predicting CD4 counts <200 cells/mm3 and <350 cells/mm3 were 9.4 %, 100 %, not measurable and 1.1, and 6.1 %, 98.8 %, 5.13 and 0.95, respectively. The association of Hb (<10,11,12 g/dl and <10,12,14 g/dl for CD4 counts <200 cells/mm3 and <350 cells/mm3, respectively), and ESR (<10, 20 and 30 mm fall after 1 hour) with these two CD4 counts cut-off values were suboptimal.

Conclusion

This study reveals the poor association of TLC, Hb, and ESR with CD4 counts in HIV infected adults, thus highlighting the need to review the utility of these surrogate markers, for predicting CD4 counts in people living with HIV/AIDS.

Introduction

As per the 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS among adolescents and adults [1], the clinical importance of CD4 counts in HIV-disease staging has been emphasized.

The World Health Organization (WHO) currently recommends initiation of antiretroviral therapy (ART) in people living with HIV/AIDS (PLHA) with CD4 T-lymphocyte counts <350 cells/mm3 irrespective of the WHO clinical staging [2]. In India, however, as per the National AIDS Control Organization (NACO) recommendations, initiation of ART should be considered if CD4 cell counts are less than 350/mm3 and in those with symptomatic HIV disease and CD4 cell counts between 200-350/mm3 [3].

Obtaining CD4 counts requires the use of expensive tools, which are not readily available in resource-limited settings. The identification of laboratory tests that help the clinician to predict progression is useful not only to monitor the patients’ disease evolution but also to define the appropriate time to initiate treatment.

According to the WHO guidelines [4], in the absence of CD4 counts, total lymphocyte count (TLC) <1200/mm3, though a less useful substitute, can be used for starting ART in individuals with symptomatic HIV disease. There are studies in HIV-infected adults that have demonstrated association of TLC <1200/mm3 and subsequent disease progression or mortality [5, 6, 7] as well as those which propose that the rate of TLC decline should be used in disease monitoring [7, 8]. However, it is important to note that the WHO continues to recommend CD4 count as the main laboratory measurement for making decisions about when to start, stop, and change ART [4].

There are studies which have investigated the association of other surrogate markers such as haemoglobin (Hb), and erythrocyte sedimentation rate (ESR) with CD4 count and disease progression. In a study from Africa, ESR has been demonstrated to have a strong negative association with CD4 count [9]. While the rates of decrease in Hb have been reported to correlate with falling CD4 counts [5, 6], there have been suggestions that increases in haemoglobin are predictive of treatment success when combined with an increase in TLC [8].

This study aimed to find out the relationship of CD4 counts with TLC, Hb and ESR and whether these parameters can be used as substitute surrogate markers for CD4-positive T lymphocyte counts in HIV-infected individuals.

Section snippets

Material And Methods

The study was a cross sectional pilot study, wherein the participants were HIV-1 positive adults admitted to, or attending outpatient departments at a tertiary care hospital between May and July 2009 (n=215). Those HIV-1 infected individuals who were previously ART-experienced were excluded from the study.

The blood and serum samples were collected after obtaining informed consent. The TLCs of study participants were measured using the Beckman Coulter AcT Diffuse II Haematology Analyzer.

Results

The study population comprised of 215 HIV-1 infected adult individuals of whom 179 were males and 36 females. The median age of the study population was 35 years (range: 24-60 years).

The scatter diagram in Fig. 1 depicts the distribution of the CD4+ T lymphocytes when plotted against the TLCs, Hb levels and ESRs of the study participants.

Spearman's rank order correlation was applied as a statistical test of significance on the different study population categories based on their respective CD4+

Discussion

Spacek et al [12] (2003) studied the ability of TLC and Hb to predict CD4 count. A total of 3,269 individuals from the Johns Hopkins HIV Observational Cohort were evaluated retrospectively. While the cut off values for TLC below 1200 cells/mm3 and haemoglobin below 12 g/dl significantly predicted CD4 cell counts below 200 cells/mm3, for TLC alone, the sensitivity and specificity were reported as 70.7 and 81.7%, respectively. This study concluded that TLC <1200 cells/mm3 was associated with CD4

Conflicts of Interest

Part of this research work was submitted as a Maharashtra University of Health Sciences, Nashik sponsored short term research studentship project report by Dr Akshat Vyas under the discipline of Microbiology under the guidance of Lt Col S Sen.

Intellectual Contribution of Authors

Study Concept: Lt Col Sourav Sen, Lt Col Sunil Sanghi, Col K Shanmuganandan, Col RB Batra

Drafting & Manuscript: Lt Col Sourav Sen, Surg Cmde AK Praharaj, Brig Ketoki Kapila, Col RM Gupta, Akshat Vyas, Col Satish Kumar

Statistical Analysis: Lt Col Sourav Sen

Tecnical Support: Lt Col Sourav Sen, Col RB Batra

Study Supervision: Lt Col Sourav Sen, Brig Ketoki Kapila

Acknowledgements

The authors thank Mr. D.R. Basannar, Scientist E and Mrs. Seema Patrikar, Department of Community Medicine, Armed Forces Medical College, Pune, for providing guidance on statistical analyses.

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